Reduced colitis-associated colon cancer in Fat-1 (n-3 fatty acid desaturase) transgenic mice. Academic Article uri icon

abstract

  • Bioactive food components containing n-3 polyunsaturated fatty acids (PUFA) modulate multiple determinants that link inflammation to cancer initiation and progression. Therefore, in this study, fat-1 transgenic mice, which convert endogenous n-6 PUFA to n-3 PUFA in multiple tissues, were injected with azoxymethane followed by three cycles of dextran sodium sulfate (DSS) to induce colitis-associated cancer. Fat-1 mice exhibited a reduced number of colonic adenocarcinomas per mouse (1.05 +/- 0.29 versus 2.12 +/- 0.51, P = 0.033), elevated apoptosis (P = 0.03), and a decrease in n-6 PUFA-derived eicosanoids, compared with wild-type (wt) mice. To determine whether the chemoprotective effects of n-3 PUFA could be attributed to its pleiotropic anti-inflammatory properties, colonic inflammation and injury scores were evaluated 5 days after DSS exposure followed by either a 3-day or 2-week recovery period. There was no effect of n-3 PUFA at 3 days. However, following a 2-week recovery period, colonic inflammation and ulceration scores returned to pretreatment levels compared with 3-day recovery only in fat-1 mice. For the purpose of examining the specific reactivity of lymphoid elements in the intestine, CD3(+) T cells, CD4(+) T helper cells, and macrophages from colonic lamina propria were quantified. Comparison of 3-day versus 2-week recovery time points revealed that fat-1 mice exhibited decreased (P < 0.05) CD3(+), CD4(+) T helper, and macrophage cell numbers per colon as compared with wt mice. These results suggest that the antitumorigenic effect of n-3 PUFA may be mediated, in part, via its anti-inflammatory properties.

published proceedings

  • Cancer Res

altmetric score

  • 3

author list (cited authors)

  • Jia, Q., Lupton, J. R., Smith, R., Weeks, B. R., Callaway, E., Davidson, L. A., ... Chapkin, R. S

citation count

  • 118

complete list of authors

  • Jia, Qian||Lupton, Joanne R||Smith, Roger||Weeks, Brad R||Callaway, Evelyn||Davidson, Laurie A||Kim, Wooki||Fan, Yang-Yi||Yang, Peiying||Newman, Robert A||Kang, Jing X||McMurray, David N||Chapkin, Robert S

publication date

  • May 2008